To study the significance of c-myc, p53 and p16 protein expression in fibrous dysplasia, to detect the GNAS1 gene mutation in fibrous dysplasia, and to explore the property of fibrous dysplasia.The expression of c-myc, p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy, 1 Mazabraud syndrome and 20 control cases (10 cases of bony callus, 10 cases of osteosarcoma). Genomic DNA extraction, PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia.C-myc protein immunoreactivity was detected in 91 percentage of FD (P = 0.001). Compared with the negative control group, the difference was significant. P16 positive was detected in 34 FD cases (P = 0.001). The difference was significant as compared with the positive control group. Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation. PCR amplification was successful in 12 of 35 FD cases. Two of the 12 FD cases were detected to have GNAS1 gene mutation, in which 1 case was FD of Mazabraud syndrome, 1 case was a monostotic lesion.C-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease. P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD. The abnormal expression of the gene p16 might play an important role in the formation of FD. The GNAS1 mutation exist in FD. All of the results indicate that FD could be a neoplasia disease, caused by multiple factors leading to a dysfunction of bone development.